Confinement of fluids on surfaces

ABSTRACT

The invention is directed to a device for applying a fluid to a surface, the device comprising a first conduit for directing a flow of a first fluid towards the surface and a second conduit for directing a flow of a second fluid away from the surface, the first conduit being arranged relative to the second conduit such that in operation of the device the second fluid comprises substantially the first fluid, and wherein said first conduit comprises a first aperture and the second conduit comprises a second aperture, the first aperture arranged at a distance from the second aperture.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.10/841,390, filed May 7, 2004, incorporated by reference herein.

FIELD OF THE INVENTION

The present invention generally relates to confinement of fluids onsurfaces and particularly relates to methods and apparatus for applyingand confining fluids to surface areas. Even more particularly theinvention relates to locally processing a surface for both additive andsubtractive patterning of materials while the surface is immersed in afluid.

BACKGROUND OF THE INVENTION

There are many applications in which it is desirable to apply a fluid toa surface. An example of such an application is in patterning or otherprocessing of surfaces. Patterning and processing of surfaces withfluids is becoming increasingly important in a range of fields,including chemistry, biology, biotechnology, materials science,electronics, and optics. Patterning a surface by applying a fluid to thesurface typically involves confinement of the fluid to defined regionsof the surface.

A surface is typically wettable by a fluid if the contact angle betweena drop of the fluid and the surface is less than 90 degrees. A channelfor carrying a fluid is typically wettable if the channel exerts anegative pressure on the fluid when partially filled. Such a negativepressure promotes filling of the channel by the fluid. In a channelhaving a homogeneous surface, a negative pressure arises if the contactangle between the fluid and the surface is less than 90 degrees. Asurface is typically regarded as being more wettable if the contactangle between the surface and the fluid is smaller, and less wettable ifthe contact angle between the surface and the fluid is higher.

One conventional surface patterning technique is lithography. Inlithography, a mask is usually applied to a surface to be patterned.Apertures are formed in the mask to define regions of the surface to beexposed for treatment. Areas of the surface remaining covered by themask are protected from treatment. The mask is typically formed from apatterned layer of resist material. The surface carrying the mask maythen be immersed in a bath of chemical agents for treatment of theexposed regions. Lithography is a relatively expensive process toperform, involving multiple steps, expensive instruments and laboratoryfacilities with controlled environments. With the possible exception ofin situ synthesis of short deoxyribonucleic acid (DNA) strands,lithography is generally unsuitable for handling and patterningbiomolecules on surfaces. Lithography is also unsuitable forsimultaneously processing surfaces with different chemicals in parallel,as described by Whitesides, Annu. Rev. Biomed. 3 (2001), 335-373. Therecan be incompatibility between different process steps or chemicals usedin lithography and between various surface layers processed bylithography.

Another conventional surface patterning technique is drop delivery. Dropdelivery systems, such as pin spotting systems, ink jet systems, and thelike, typically project a relatively small volume of fluid onto aspecific location on a surface. See, M. Shena, “Microarray BiochipTechnology,” Eaton Publishing (2000). However, these systems havelimited resolution due to spreading of dispensed drops on the surface.Additionally, the quality of patterns formed by such systems is limitedby drying of the delivered fluid, as is described by J. T. Smith,Spreading Diagrams for the Optimization of Quill Pin Printed MicroarrayDensity, 18 LANGMUIR 6289-293 (2002). Further, these systems aregenerally not useful for dissolving or extracting materials from asurface, do not facilitate a flow of fluid over a surface and are notsuited to process a surface sequentially with more than one fluid.

PCT WO 01/63241 A2 describes a surface patterning technique involvinguse of a device having a channel with a discharge aperture. A matchingpillar is engaged with the discharge aperture to promote deposition ofmolecules on a top surface of the pillar. However, it is not possible tovary patterning conditions for different pillars individually. Exposureof the pillar surface to the fluid should be long enough to allowreagents to reach the surface by diffusion. The method also requires asurface with pillars matching the aperture. Precise alignment of thedevice with the pillars before engagement is required. Spacing betweenthe discharge aperture and the pillars needs external control. Thepillars cannot be moved on the surface to draw lines.

Another conventional surface patterning technique involves applicationof a microfluidic device to a surface. An example of such a device isdescribed in U.S. Pat. No. 6,089,853 issued to Biebuyck et al.(hereinafter “Biebuyck”). The microfluidic device can establish a flowof fluid over a surface. The flow can be created via capillary action inthe device. The device can be used to treat a surface with differentfluids in parallel. However, the device must be sealed to the surface tobe treated to confine the fluid(s) to the region(s) of the surface to betreated. Confinement of the fluid(s) allows for the formation ofpatterns with relatively high contrast and resolution. High contrast andresolution are desirable qualities when biomolecules are patterned on asurface for biological screening and diagnostic purposes.

The device is placed on the surface to be treated and sealed around theprocessing regions before being filled with treatment fluid. However, ifthe flow is created by capillary action, several notable disadvantagesresult. First, service ports in the device must be filled with treatmentfluid for each patterning operation. Also, only one fluid can bedelivered to each channel in the device and cannot be flushed out of thechannels before separation of the device from the surface. Further, thefluid tends to spread away from the regions of the surface to be treatedduring removal of the device from the surface. Therefore, the device isnot suitable for processing a surface sequentially with several fluids.

If the flow is created by external actuation, such as by pressurization,electric fields, or the like, several other notable disadvantagesresult. For example, an individual connection from the actuator must bemade to each channel in the device. These connections, e.g., toperipheral equipment, limit the density of channels that can beintegrated into the device and addressed individually. Pumping, valvingand control complexity increase as the number of channels increases.External connections create dead volume between the device and externalactuators because of the intervening conduits.

Another microfluidic device for localized processing of a surface isdescribed in IBM Technical Disclosure Bulletin reference RD n446,Article 165, Page 1046. The device is similar to that described inBiebuyck. It permits several fluids to be flushed in sequence over thesame surface area without requiring separation of the device from thesurface. Such a device is thus useful for chemical and biologicalreactions involving the sequential delivery of several fluids. However,the device must be sealed around the surface to be treated beforefilling. Further, the fluids cannot be filled prior to the device beingapplied to the surface. Each additional step requires supplementaryfilling of the relevant fluid. Further, the lines in the device need tobe prestructured via lithography and cannot be readjusted subsequently.

Another conventional device for confining fluids to a predefined patternbetween a top and bottom surface without involving a seal is describedin European Patent 0 075 605. This device is useful for performingoptical analysis of the confined fluid. However, the device requirespredefined topographical or chemical patterns on both the top and bottomsurfaces. Also, the device, having no inlet or outlet ports, is notsuitable for the transport of fluids.

Another device for guiding fluids along a predetermined path isdescribed in WO 99/56878. This device can flow several fluidssimultaneously over a surface without involving a seal to confine thefluids. However, separation gaps between the paths have to be capillaryinactive. This limits path sizes to greater than one millimeter (mm).Otherwise, meniscus pressures produce uncontrolled spreading of thefluids. Further, the fluid is not retained after separation and caninstead spread over the surface, fluid delivery requires an externalconnection to each path and cumbersome peripheral flow control devicesare required.

Yet another method for guiding fluid along a surface without involving aseal is described in B. Zhao et al., Surface-Directed Liquid Flow InsideMicrochannels, 291 SCIENCE 1023-26 (2001). In this method, a surface ispatterned with a wettability pattern. Specifically, two wettablepatterns mirroring each other are defined on otherwise non-wettable topand bottom surfaces. This produces “virtual” channels without lateralwalls, that can have a micrometer width. However, this method requireswettability patterns on both the top and bottom surfaces. In otherwords, the path for the flow of fluid must be predetermined usinglithography, which is expensive and lacks flexibility. Furthermore,subsequent readjustment of the flow paths cannot be performed.

Further, the contrast in wettability between the two patterns needs tobe very high, both non-wettable areas are required on both the top andbottom surfaces and highly wettable areas are required within thevirtual channel. The two patterns have to match each other exactly inshape and alignment. Capillary action can be used to fill the channels,but the fluid cannot be removed or exchanged. This method is alsosusceptible to uncontrolled spreading of fluid because it is relativelydifficult to produce sufficiently non-wettable surfaces.

A double pipette system might be employed for local controlled druginfusion. See for example, O. Feinerman, A Picoliter “Fountain Pen”Using Co-Axial Dual Pipettes, 127 JOURNAL OF NEUROSCIENCE METHODS 75-84(2003). Namely, two concentric pipettes can be manipulated separatelyand pressurized independently by a designated double holder. The innerpipette is loaded with a desirable solution, and functions as a source,while the outer pipette serves as a sink. This configuration providesfor a flow of solution between the two pipettes that protrudes only asmall distance into the surrounding fluid and does not diffuse away.However, without moving the pipette the infusion only occurs onlybriefly and does not allow for the creation of a two-dimensionalpattern.

In WO 01/49414 a dual capillary system is described that can be used toprovide a resolubilizing fluid onto a surface of a substrate. A secondcapillary element is then used to draw the material from the surface ofthe substrate into the analysis channel of a microfluidic device. Thecapillaries are disposed adjacent to one another such that fluid isdelivered from one capillary and drawn up into, e.g., sampled by, theother capillary without moving the microfluidic device or the substrate.Fluid is expelled from the fluid delivery capillary onto a samplematerial surface whereupon the sample material is at least partiallyresolubilized in the expelled fluid. A portion of the fluid on thesubstrate with the resolubilized sample material is then drawn into theanalysis channel.

This system is designed to have the smallest distance possible betweenthe capillaries such that the resolubilized sample material in theexpelled fluid is received close to the fluid delivery capillary. Thedual capillary system is not be moved over the sample surface duringeither delivery or sampling of the fluid. For this resolubilizingtechnique to function properly, there is to be some delay betweendelivery and sampling of the fluid. Further, sampling comprises drawingonly a portion of the resolubilized material into the samplingcapillary.

Therefore, it would be desirable to provide a technique for confining afluid on a surface in a manner that allows the technique to be used tocreate two-dimensional patterns.

SUMMARY OF THE INVENTION

According to a first aspect of the present invention, a device isprovided for applying a fluid to a surface, also referred to as fluidpattern creator. The device comprises a first conduit for directing aflow of a first fluid towards a surface and a second conduit fordirecting a flow of a second fluid away from said surface. The firstconduit is arranged relative to the second conduit such that inoperation the second fluid comprises substantially the first fluid, andwherein the first conduit has a first aperture that is arranged at adistance from a second aperture of the second conduit. The firstaperture is also referred to as discharge aperture, the second apertureis also referred to as aspirator aperture.

This device allows for the hydrodynamical confinement of the flow of aprocessing fluid between the discharge aperture, the aspirator apertureand a surface. Thereby a pattern can be created that corresponds to theflow path of the first fluid from the first conduit towards the secondconduit. This technique is feasible even at micrometer resolution. Thisfluid pattern creator can also be used to confine and transport thefirst fluid over a surface that is immersed in the same or a differentfluid, and can find application in surface and/or particletreatment/patterning for, e.g., microelectronics, optics, biology andbiochemistry.

In a preferred embodiment, the fluid pattern creator may comprise afirst fluid container for the first fluid and/or a second fluidcontainer for the second fluid. Having a first fluid container and/or asecond fluid container makes the fluid pattern creator independent froma remote fluid container, allowing the fluid pattern creator to be usedin a more mobile manner.

In another preferred embodiment, the fluid pattern creator may furthercomprise a first flow controller for controlling a first flowrate or afirst pressure of the first fluid and/or a second flow controller forcontrolling a second flowrate or a second pressure of the second fluid.The flow controller(s) can be used to control fluid flow, for example,to increase the amount of fluid per unit time that comes in contact withthe surface, or to reduce the amount of fluid, other than the firstfluid, that is contained in the second fluid.

The fluid pattern creator may preferably be set up in such a way thatthe first and second pressures are tuned to draw the first fluid towardsthe second aperture. Drawing the first fluid towards the second apertureincreases the precision of the pattern created.

If the fluid pattern creator comprises a filter for regenerating thefirst fluid from the second fluid, the resulting first fluid can bereused for patterning, thus reducing the amount of wasted fluid. In thisexemplary embodiment, a container for the first fluid can be smaller,since it needs to store a lesser volume of first fluid.

If the conduits are arranged at an applicator head the head may bepositionable near the surface via head controllers, allowing moreflexibility in handling devices with a surface to be patterned. Inparticular the fluid pattern creator could comprise a means, e.g.,drive, for moving the applicator head relative to the surface. Beingable to move the applicator head allows for easier positioning duringcreation of a desired pattern. Namely, it allows for movement of theapplicator head during patterning, allowing for the creation of a largervariety of patterns.

If at least one of the apertures of the conduits is arranged in a recessof the applicator head, the flow of the fluid can be better controlledand decoupled from an environmental fluid. In a preferred embodiment,the first and the second aperture are arranged in the recess, serving asa flow path. In this embodiment, the flow path is not straight, e.g.,curved. The form of the recess shapes the form of the flow path. Whenthe flow path is not straight, a larger variety of patterns can beobtained without active flow-path-shaping means.

If the first aperture and the second aperture are arranged at asubstantially identical distance from the surface, the flow of the firstfluid towards the second aperture (i.e., from the first aperture) willbe homogeneous, thereby allowing for an accurate determination of anamount of the first fluid coming into contact with the surface. Theability to accurately determine this amount is beneficial for assessingchemical interaction between the first fluid and the surface.

In an exemplary embodiment, a third conduit is arranged for directingthe flow of a third fluid in such a way that the flow of the third fluidinfluences the flow direction of the first fluid. The third fluid can beselected to be an influencer, acting as an active forming means for theflow path, and/or to have a predetermined reactive characteristic,allowing the third fluid to become a part of the patterning process. Forinstance the third fluid can react with the first fluid, rendering thefirst fluid weaker or stronger, and thus changing the intensity ofreaction and the pattern that is eventually created. The third fluid canalso react with the surface to modify the pattern created by the otherfluid(s).

The fluid pattern creator preferably comprises a distance element fordetermining the distance between the apertures and the surface. Thisdistance element provides an efficient means to ensure that the distancebetween the apertures and the surface is kept constant. Maintaining aconstant distance between the apertures and the surface results in amore predictable pattern.

If the fluid pattern creator comprises a unitary construction, e.g.,manufactured from a single piece of material, the fluid pattern creatoris both robust and more easily produced. At the same time, mechanicaltolerances are not a critical issue, the resulting fluid pattern creatorexhibits a higher degree of precision and alignment that is achievable.Alignment is a critical issue to create precise patterns on a surface.

In an exemplary embodiment, the first pressure is tuned such that thefirst fluid is retained in the first fluid container when the firstaperture is remote from the surface. When the first aperture is moved tobe proximal to the surface, pressure may be varied, e.g., applied, toinitiate flow of the first fluid out of the first aperture and onto thesurface. When the device is withdrawn from the surface, the firstpressure may then again be tuned to draw back excessive fluid from thesurface. Further, there may be a plurality of first fluid containers,each coupled to the first aperture, wherein the pressure for the firstfluid in each of the plurality of first fluid containers is controlled,in parallel or individually.

The first or second pressure may be generated by external pumps, such assyringe pumps or peristaltic pumps, by integrated pumps, such asmicrofabricated pumps, by electro-kinetic pumping, by capillary-forcebased pumping, by other pumping means or by other means ofpressurization. Further, valves may be provided for controlling theflowrate of the first or second fluid. Such valves may be located withinexternal connections, in the fluid container, in the connections betweenthe fluid container and the aperture or in the aperture. Such valves maybe closed or opened on demand.

The present device, as described herein, may be part of a fluidicnetwork. In such a fluidic network, there may be a feedback system formeasuring the network pressure, for example, the pressure at theapertures and/or at the fluid containers. Alternatively, feedback may beprovided based on the volume of fluid pumped. The feedback facilitatesfluid flow control to avoid undesired spreading of fluid on the surface.When a plurality of fluid containers are present, each coupled to anaperture, pressure may be controlled in each fluid container, either inparallel or individually. Further, one or more valves may control theflow for each fluid container, either in parallel or individually (e.g.,through use of a flow controller).

The flow controller may apply a pressure for retaining the fluid whenthe aperture is remote from the surface. The flow controller may alsocomprise a capillary network for applying pressure to the fluid. Thiscapillary network may comprise one or more parallel capillary members, amesh, a porous material and a fibrous material. There may be a pluralityof fluid containers each coupled to an aperture. The pressures appliedmay be such that the fluid is drawn towards the fluid containers inresponse to withdrawal of the aperture from the surface. There may be aplurality of first and second fluid containers, each coupled to theaperture, wherein the pressure is controlled in each fluid container,either in parallel or individually.

The pressure for the first fluid container may be regulated such thatthe first fluid is retained in the first aperture when the flow path isremote from the surface. Pressure for the second fluid container mayalso be regulated such that the difference between the first and secondpressures is oriented to promote flow of the first fluid from the firstfluid container to the second fluid container, via the flow path, whenthe flow path is located proximal to the surface (the first fluid in thedevice contacting the surface). The first and second pressures canfurther be regulated such that excessive fluid is drawn towards at leastthe second fluid container in response to withdrawal of the flow pathfrom the surface. There may be a plurality of first fluid containerseach coupled to the flow path. Similarly, there may be a plurality ofsecond fluid containers each coupled to the flow path.

As described above, the pressure in the first and second aperture may begenerated by, e.g., external pumps. A feedback system may be providedthat measures the pressure within the system, for example at the firstand second aperture and/or at the first and second fluid container. Thefeedback system may be based on the volume of fluid pumped in the firstand second fluid container. Employing this feedback system canfacilitate control of the fluid flow and prevention of undesiredspreading of fluid on the surface. There may be a plurality of first andsecond fluid containers each coupled to first and second apertures,where pressure is controlled in each of the first and second apertures,either in parallel or individually. Further, there may be one or morevalves, controlling flow for each of the first and second apertureseither in parallel or individually. There also may be a plurality offirst fluid containers each coupled to the flow path and/or a pluralityof second fluid containers each coupled to the flow path.

In an exemplary embodiment of the present invention, the first flowcontroller applies a first pressure for retaining the fluid when theflow path is remote from the surface. The second flow controller appliesa second pressure to the second fluid such that the difference betweenthe first and second pressures is oriented to promote flow of the firstfluid from the first fluid container to the second fluid container viathe flow path, in response to the flow path being located proximal tothe surface and the fluid in the device contacting the surface. Manyother applications of the present invention are possible.

As mentioned above, the device may comprise a unitary construction, andmay be formed from materials that include, but are not limited to,elastomer, silicon, SU-8, photoresist, thermoplastic, ceramic, metal,and combinations comprising at least one of the foregoing materials.Alternatively, the device may comprise a layered construction, with eachlayer formed from materials that include, but are not limited to, glass,polymer, silicon, SU-8, photoresist, thermoplastic, metal, ceramics andcombinations comprising at least one of the foregoing materials.

As mentioned above, the present devices are particularly useful fortransporting a first fluid from a fluid container, well, reservoir, orsimilar fluid container, to a surface, and to confine the first fluid onthe surface without the need for a physical seal between the device andthe surface. Accordingly, each aperture of the device may be defined byand comprise non-sealing materials, including, but not limited to,silicon. The non-contact operation of the present device preventscontamination and/or damage to the surface being treated and/or to thedevice.

The present treatment techniques are applicable to surfaces having awide range of different properties and wettability. The present devicepermits addition of a flow of first fluid, thus preventing depletion ofmaterial adsorbed to the surface treated. Homogeneous patterns of, forexample, biomolecules may be thereby produced. When the present deviceis traced over the surface to be treated, the lines produced aresmoother and smaller than those attained using conventional techniques,such as ink jet printing. For example, if the amount of the first fluiddeposited is relatively small, there is little if any no spreading,quick drying and no excessive accumulation of material on the surface.

According to the present techniques, the concentration of depositedmaterials may be varied as the device is drawn over the surface treated.A range of gradients in concentration of deposited materials may thus beproduced. Therefore, such a device is useful for both additive andsubtractive patterning of materials onto a surface. Further, a series ofsuch devices may be drawn over a surface in sequence. Each aperture ofsuch a series of devices may contain a different one of a potentialgroup of reagents for collectively implementing a chain reaction on thesurface.

According to the teachings of the present invention, the device(s) canbe pre-filled with processing fluids for subsequent repetitiveapplication and surface removal during processing. Surface processingcan be repeated multiple times using the same device without refilling(which can delay the process). The present device can also be swiftlymass-produced via conventional microfabrication techniques. In typicalapplications, the present device can be placed at an arbitrary locationon a surface and process parameters can be controlled via dimensions andcontact time. Arrays of such devices are relatively easy to fabricate.

The present devices are suitable for treating curved surfaces, such asbeads or cylinders, inhomogeneous surfaces, surface with variablewettability, corrugated or otherwise roughened surfaces and the like.Further, the present device may be employed to deposit biomolecules inselected regions of a surface, e.g., to make bio-arrays, thusfacilitating mass fabrication of bio-chips. The present device may alsobe employed in subjecting selected areas of a surface to otherprocesses, including, but not limited to, processes for repairingpattern defects on a surface, etching specific areas of a surface,depositing metal on a surface, localizing an electrochemical reactionson a surface, depositing catalytic particles for electroless depositionof metals, deposition glass or latex beads or other particles on asurface, passivating specific areas of a surface, patterning proteins,deoxyribonucleic acid (DNA), cells, or other biological entities on asurface, making assays and staining cells.

The present device may be operated facing upwardly towards a downwardfacing surface, especially when the dimensions of the device are chosento be small, such that forces in the fluid interface exceed inertialforces. In general, gravity has a limited effect on the device such thatuse of the device in reduced gravity environments is possible.

In one aspect of the present invention, a two aperture applicator headis located proximal to the surface. A first fluid is supplied to thesurface via the applicator head. The applicator head is then retractedfrom the surface.

During supplying the first fluid, the first fluid flows from the firstfluid container to the second fluid container via the flow path. Theflow of the first fluid from the first fluid container to the secondfluid container may be varied during the supply of the first fluid tothe surface. Prior to retracting the applicator head, the applicatorhead may be moved relative to the surface, with the first fluid in oneor more of the apertures contacting the surface.

The applicator head may be oriented relative to the surface such thattraces of the fluid produced as the applicator head is moved relative tothe surface remain separate, or alternatively, overlap. Prior tolocating the applicator head proximal to the surface, the same fluid maybe loaded into each of the fluid containers. Alternatively, one or moredifferent fluids may be loaded into one or more of the fluid containers.

Further disclosed herein is a method for applying a fluid to a surfacecomprising the following steps. An array of applicator heads is locatedproximal to the surface. A first fluid is supplied to the surface viathe array. In each applicator head of the array, the first fluid isflowed from the first fluid container to the second fluid container viaa flow path. The array is moved relative to the surface with the firstfluid in each aperture contacting the surface. The array is thenretracted from the surface.

In at least one applicator head of the array, the flow of the firstfluid from the first fluid container to the second fluid container maybe varied during the supply of the first fluid to the surface. The arraymay be oriented relative to the surface in a way such that traces of theflows of first fluid produced as the array is moved relative to thesurface remain separate, or alternatively, overlap. Similar or differentfirst fluids may be loaded into each applicator head of the array.

In one embodiment of the present invention, an applicator head isbrought close to a surface so as to contact the surface with the fluidin an area of micrometer dimensions defined by the geometry of theaperture. The applicator head is then removed from the surface. Prior tothe removal of the applicator head, the surface may be moved laterallyrelative to the applicator head with the first fluid in the applicatorhead remaining in contact within the surface so that the first fluid istraced across the surface. Alternatively, the tracing may be performedusing the applicator head and having the first fluid flowing between theapertures as the applicator head is traced is over of the surface.

A more complete understanding of the present invention, as well asfurther features and advantages of the present invention, will beobtained by reference to the following detailed description anddrawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a cross-sectional side view/functional diagram of a fluidapplicator with a concentrical arrangement of conduits;

FIG. 2 a is across-sectional view of an applicator head with a firstconduit arranged at a distance from a second conduit;

FIG. 2 b is a plan view of the bottom surface of the applicator headshown in FIG. 2 a;

FIG. 3 is a plan view of the bottom surface of an applicator head withmore than two conduits;

FIG. 4 is a cross-sectional view/downside view of an applicator headwith two apertures within an arc-shaped recess;

FIG. 5 is a plan view of the device shown in FIG. 3 operating in adrawing mode;

FIG. 6 is a plan view of a surface treated by the drawing operationshown in FIG. 5;

FIG. 7 is a plan view of a multi-path device operating in a drawingmode; and

FIG. 8 is a plan view of a surface treated by the drawing operationshown in FIG. 7.

All the figures are for sake of clarity not shown in real dimensions,nor are the relations between the dimensions shown in a realistic scale.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

Referring first to FIG. 1, a substrate having an upper surface 11,carries on surface 11 a fence 21 that surrounds a space filled with anenvironmental fluid 20. A fluid applicator comprises a first fluidcontainer 9 that is connected via a first flow controller 7 to a firstconduit 1 having a first aperture 18 arranged in proximity to thesurface 11. A second fluid container 10 is connected via a second flowcontroller 8 to a second conduit 2 having a second aperture 19 arrangedin proximity to the surface 11, and surrounding said first aperture 18.The second fluid container 10 is connected via a filter 13 to the firstfluid container 9. The first fluid container 9 holds a first fluid 3that is movable through the first conduit 1 towards the first aperture18, and from there directable towards the surface 11. The secondaperture 19 provides a flow of a second fluid 4 away from the surface 11through the second conduit 2 into the second fluid container 10.

This arrangement allows for the creation of a fluid flow out from thefirst conduit 1 alongside the surface 11 and into the second conduit 2.This arrangement can be used to modify the surface 11, for instance byselecting as the first fluid 3 an acid that etches the surface where theacid impinges onto the surface 11, thereby creating an etched pattern12. The second fluid 4 will be composed of a part of the first fluid 3and of the environmental fluid 20.

The first flow controller 7 and the second flow controller 8 arefunctional to control the speed of flow through the correspondingconduits 1, 2. The filter 13 may be employed to recover the first fluid3 from the second fluid 4. The first flow controller 7 is arranged forcontrolling a first flow rate and/or a first pressure p3 of the firstfluid 3. The second flow controller 8 is arranged for controlling asecond flow rate and/or a second pressure p4 of said second fluid 4.

Referring next to FIG. 2 a, an applicator head 15 is depicted, theapplicator head 15 comprising a block of solid material having twoopenings, one for the first fluid container 9 and one for the secondfluid container 10. The first fluid container 9 is again connected to afirst conduit 1 through which a first fluid 3 is deployable to a surface11 for creating a pattern 12 thereon. The second fluid container 10 isagain connected to a second conduit 2 through which a second fluid 4 ismovable into the second fluid container 10 away from the surface 11. Theend of the first conduit 1 proximal to the surface 11 is the firstaperture 18, while the end of the second conduit 2 proximal to thesurface 11 is the second aperture 19. Both apertures 18 and 19 arearranged at a distance d from each other. Thus, the first fluid 3 whenexiting from the first aperture 18 and when being drawn towards thesecond aperture 19, moves along an elongated flow path between theapertures 18 and 19.

The pattern that is created on the surface 11 corresponds to the form ofthe flow path. Hence, with this applicator head 15, patterns can becreated that are not point-formed (as compared with the results of theapparatus shown in FIG. 1). The flow rate of the second fluid 4 can becontrolled in a way that most, or even all, of the first fluid 3 isdragged into the second aperture 19, thereby reducing a blurring of thepattern through contact between the surface 11 and the first fluid 3 atlocations outside the desired pattern area. The second aperture 19 canbe designed to be larger than the first aperture 18 to enhance thiseffect.

FIG. 2 b shows a bottom view of this applicator head 15, also depictinga possible form of the pattern 12 that may be created therewith. Theapplicator head 15 is combinable with the arrangement from FIG. 1,replacing the coaxial arrangement of conduits. Hence, the applicatorhead 15 may be modified to comprise also a first flow controller 7 and asecond flow controller 8. The applicator head 15 may also be modified tonot comprise the first fluid container 9 and the second fluid container10, but instead be connectable to the first fluid container 9 and thesecond fluid container 10, e.g., as depicted in FIG. 1.

The first aperture 18 and the second aperture 19 of the applicator head15 can be brought close to the surface 11 immersed in the environmentalfluid 20, to be treated. The first flow controller 7 is usable todispense the first fluid 3 through the first aperture 18 such that thefirst fluid 3 contacts the surface 11. Simultaneously, the second flowcontroller 8 can aspirate the second fluid 4 at a second flow rate equalto or larger than the first flow rate of the first flow controller 7.This can be achieved by setting the first pressure p3 lower in absolutevalue than the second pressure p4. The flow rates are preferably chosensuch that the first fluid 3 dispensed from the first aperture 18 isaspirated back into the second aperture 19, with little or no leakage ordiffusion of the first fluid 3 into the bulk of the environmental fluid20.

It is advantageous to choose a dispense rate that results in laminarflow (such flows being typical for small dimensions). With laminar flow,there are less turbulences that could mix the dispensed first fluid 3with the surrounding environmental fluid 20 and thus can effectivelyprevent leakage of the first fluid 3. The first fluid container 9 isloaded with the fluid 3 to be dispensed onto the surface 11 to betreated.

The surface 11 may be a glass surface. However, the surface 11 may haveother forms. For example, the surface 11 can be flat, rough, corrugated,porous, fibrous, and/or chemically inhomogeneous.

In operation, the first aperture 18 is brought proximal to the surface11. By tuning the first pressure in the first fluid container 9, thefirst fluid 3 contacts the surface 11. Active flow controllers such asexternal pumps, integrated pumps and valves may be provided to regulatethe pressure in the fluid container 9.

The supply of the first fluid 3 can be replenished as necessary via thefirst fluid container 9. Such replenishing permits repetitive reuse ofthe device. The first fluid container 9 may be loaded and/or unloadedwith the first fluid 3 from below via the first aperture 18. A lid maybe provided to close the first fluid container 9. The lid may bepermanently sealed so that the first fluid 3 can only be introduced viathe first aperture 18. The first aperture 18 may be likewise providedwith a lid to prevent evaporation, e.g., during periods of non-use. Asupport device having a reservoir for the first fluid 3 may be providedfor filling, refilling and draining the first fluid container 9 withoutinvolving removal of the lids.

The first fluid 3 may contain treatment agents for processing a regionof the surface 11. Engaging the device with the surface 11 causesexposure of the region of the surface 11 facing the first aperture 18 tothe treatment agent. The treatment agent may comprise molecules. Thedevice is therefore useful in bio-patterning applications. However,other applications are possible, such as sequential delivery ofdifferent treatments to the surface 11. Similarly, other fluid materialsmay be employed depending on the surface processing desired. Examples ofpossible fluid materials include, but are not limited to, etchants forproducing localized chemical reactions on the surface 11.

In FIG. 3, an arrangement of an applicator head 15 comprising more thantwo apertures is depicted. In this arrangement, to a side of the flowpath between the first aperture 18 and the second aperture 19 arearranged two additional apertures 21 and 22 each belonging to a thirdconduit 5. The third conduit 5 is here arranged to eject a third fluid 6towards the surface 11, thereby influencing the flow of the first fluid3, as indicated by the arrows in FIG. 3. The flow of the first fluid 3may be narrowed under the influence of the third fluid 6. Therefore, thethird fluid 6 serves as a forming fluid, giving the fluid flow of thefirst fluid 3 a different form and hence with it also the resultingpattern 12 on the surface 11.

At a side of the first aperture 18 distal from the second aperture 19,another additional aperture 17 may be arranged, again for ejecting thethird fluid 6, using it as forming fluid to reduce the flow of the firstfluid 3 that is directed away from the second aperture 19. At a side ofthe second aperture 19 distal from the first aperture 18, a similaraperture 16 may be arranged. All additional apertures, e.g., 16, 17, 21and 22, that belong to the third conduit 5 hence allow for the shapingof the fluid flow of the first fluid 3 towards the second aperture 19,to improve the pattern quality.

To further improve the pattern quality, the first aperture 18 and/or thesecond aperture 19 can be arranged in a recess 30, as depicted in FIG.4. The recess 30 then serves as a semi-open channel to support the shapeof the fluid flow of the first fluid 3. This configuration becomesparticularly helpful if the recess 30 has a form that is not straight,e.g., is an arc. The first fluid 3 would follow a straight path if therecess 30 were absent, but the recess 30 channels the first fluid 3 intoits form allowing the creation of a pattern that corresponds to therecess shape, e.g., the arc. The applicator head 15 may also comprisetwo distance elements 17 that, in the event that the applicator head 15is brought into contact with the surface 11, determines the minimumdistance between the first aperture 18 and/or the second aperture 19 andthe surface 11. The geometry that is present and functional to shape thefluid flow along the flow path is thus determined and fixed. Thistechnique allows for the precise calculation of the fluid flow andresulting pattern formation. The technique also allows for use of theapplicator head 15 repetitively wherein the resulting pattern will besubstantially identical on each use of the applicator head 15.

The applicator head 15 can be of unitary construction which makes itmore stable, easier to manufacture and less prone to damage. Theapplicator head 15 may be formed from elastomeric or rigid materials.Such elastomeric or rigid materials can be shaped by microfabricationtechniques such as photolithography, etching, injection molding andcombinations comprising at least one of the foregoing microfabricationtechniques. Alternatively, the applicator head 15 may be an assemblageof parts, such as a layered assembly. Each layer may be formed from adifferent material, such as, elastomer, silicon, SU-8, photoresist,thermoplastics, ceramic and metal.

There may be multiple first conduits 1 or first apertures 18 coupled toa single second aperture 19 via a common flow path. Different reactiveagents may be introduced to each of the conduits for reaction within theflow path. The flow path may thus act as a reaction fluid container.Similarly, there may be multiple second apertures 19 connected to acommon first aperture 18 via a common flow path. Further, there may bemultiple first conduits 1 or first apertures 18 connected to multiplesecond apertures 19 or second conduits 2 via a common flow path.

Multiple devices, as described herein, may be integrated to form anarray. Multiple different configurations of such an array are possible,involving different numbers of devices. The first fluid containers 9 andthe second fluid containers 10 of such arrays may be interconnected toform a cascade. Some of the interconnected fluid containers 9 and 10 mayprovide reaction fluid containers in which the first fluid reacts. Theproduct of such reactions may be analyzed in other fluid containers oron the surface 11. Such products may be used to treat or react with thesurface 11.

With reference to FIG. 5, the present device may be employed to tracedifferent fluids across the surface 11, each fluid being loaded into adifferent fluid container of the device. The applicator head 15 istherefore coupled to a drive 16, also referred to as a manipulator. Themanipulator 16 may be employed to position the applicator head 15relative to the surface 11. With the drive 16, a series of patterns canbe created one after the other. A concatenated pattern can also becreated when moving the applicator head 15 during the patterningprocess, i.e., while the first fluid 3 is flowing out of the firstaperture 18. Therefore, more complicated patterns can be created. Themanipulator 16 may be manually controlled or automatically controlledvia a programmable computer or similar electronic control system. Themanipulator 16 may act on the applicator head 15 and/or the surface 11,providing control of (either in plane and/or out of plane) translationaland/or rotational relative motions.

Referring to FIG. 6, depending the orientation and motion of theapplicator head 15 relative to the surface 11, the different firstfluids can be mixed in selected regions of the surface 11. Such mixingmay, for example, facilitate localized reactions between the firstfluids in selected regions of the surface 11. Equally the applicatorhead 15 may be employed to trace similar first fluids across the surface11 in separate trails. Depending on the orientation and motion of theapplicator head 15 relative to the surface 11, the trails can beseparate or superimposed on each other.

A plurality of applicator heads 15 may be grouped together in an array.For example, such an array may comprise two first apertures 18 extendingfrom separate first fluid containers 9. Each first fluid container 9 maycontain the same fluid material or different fluid materials. Otherarrays may comprise more than two apertures. Groups of such aperturesmay share a common fluid container.

Referring to FIG. 7, two or more such applicator heads 15 may be mountedin an array and the applicator head 15 may be employed trace a flow ofthe first fluid 3 across the surface 11. Independent control of flowrate and tracing speed permits tuning of the surface treatment appliedvia the applicator head 15. Such an array may also be employed to tracetwo fluid flows across the surface 11.

FIG. 8 depicts the resulting pattern 12 on the surface, after use of thearrangement of FIG. 7. The fluid flows may comprise the same ordifferent fluid materials. Again, depending on the orientation andmotion of the applicator head 15 relative to the surface 11, the trailsof the fluid flows can be separate or superimposed on each other.Independent control of the tracing speed and flow rate permits creationof gradients in, for example, adsorbed molecules on the surface.

In an exemplary embodiment, the flow path has the dimensions of about100 micrometers long and about 100 micrometers wide. Likewise, the firstapertures 18 may be about 100 micrometers wide. The recess 30 may bebetween about one to about ten micrometers deep. The volumes of thefluid containers 9 and 10 may be about 500 nanoliters each. However, itis to be appreciated that the dimensions provided are merely exemplaryand that different dimensions are possible.

Given the present techniques, including the present applicator head 15,it is possible to locally transport the first fluid 3 from a reservoir,i.e., the first fluid container 9, to the surface 11, and confine thefirst fluid 3 without requiring a physical seal and without requiring asurface free-energy confinement. Applicator head 15 can be used indifferent fluidic environments, e.g., the surface 11 being immersed inthe environmental fluid which can be a liquid, a gas or a mixturethereof. Thus, it is possible to use non-sealing materials such assilicon to define the discharge aperture 18, without optimizing thewettability of the apertures 18 and 19 and the applicator head 15.

The dispensed first fluid 3 is recoupable, e.g., can be reused. Firstfluid 3 prevents contaminating or damaging the treated surface 11 by aphysical contact. The flow produced by the applicator head 15 canprevent depletion of material that can otherwise occur at these smallscales. The localization of the surface treatment may go down to areasof a few micrometers and possibly even lower. This device permits thecreation of arrays of discharge/aspiration apertures at high density.When the applicator head 15 is drawn over a surface, it can producesmooth lines, which are smoother than inkjet patterns, and potentiallysmaller than inkjet lines due to the fact that the first fluid 3 doesnot spread significantly upon contacting the surface and because thereis not a large volume that dries.

If a flow is applied in conjunction with sliding, the concentration ofthe deposited material can be continuously varied, such as to producegradients. Applicator head 15 can be used for additive or subtractive(aspirator) patterning of the surface 11. If a series of applicatorheads 15 are drawn, one behind the other, each discharge aperture, e.g.,first aperture 18, can contain a “chain-reaction” reagent. In anotherapplication, several discharge apertures can be combined with a singleaspirator, i.e., second aperture 19, allowing for the performance ofcomplex processes on a region of a surface. For example, the severaldischarge apertures may contain the four nucleotide bases present in DNAwhich could be delivered in sequence, or the several discharge aperturesmay contain two components that can react together, which could forinstance be used for joining, e.g., gluing, parts together. Potentialapplications of the present techniques, include, but are not limited to,patterning of organic materials, patterning of biomaterials, locallyexposing a sub-population of fragile cells to a specific chemicaltreatment, exposing locally a sub-population of beads to a specificchemical treatment and drawing lines on surfaces in solution.

Fluid dispensed from the applicator head 15 is confined in a volumedefined by fluid flow. A physical seal between the applicator head 15and the surface, that is, the surface to be contacted by the fluid, isnot needed.

Applicator heads, such as applicator head 15, are useful in theapplication of surface treatments in a range of fields, including, butnot limited to, microelectronics, optics, biology, biochemistry andbiotechnology. The present techniques also extend to an array of suchapplicator heads 15.

There may be a feedback system for measuring pressure within such anetwork, for example at the apertures 18 and 19 and/or fluid containers9 and 10. Alternatively, there may be provided feedback based on thevolume of fluid pumped. The feedback may facilitate control of the flowof the first fluid and avoid undesirable spreading of the first fluid onthe surface. There may be a plurality of fluid containers, each coupledto an aperture, where the pressure is controlled in each fluidcontainer, either in parallel or individually. Further, there may be oneor more valves that control the flow for each fluid container inparallel or individually.

The fluid container may apply a pressure for retaining the fluid whenthe aperture is remote from the surface. The fluid container maycomprise a capillary network for applying pressure to the fluid. Thecapillary network may comprise at least one of a plurality of parallelcapillary members, a mesh, a porous material and a fibrous material.There may be a plurality of fluid containers each coupled to anaperture. The pressures may be such that the fluid is drawn towards thefluid containers in response to withdrawal of the aperture from thesurface. There may be a plurality of first and second fluid containers,each coupled to the aperture, where the pressure is controlled in eachfluid container, either in parallel or individually.

According to another exemplary embodiment of the present invention, amethod for applying a fluid to a surface is provided. The methodcomprises the steps of locating a single aperture device proximal to thesurface, supplying the fluid to the surface via the applicator head 15and retracting the applicator head 15 from the surface.

Applicator heads, such as applicator head 15, embodying the presentinvention may be employed to deposit biomolecules in selected regions ofa surface to make bio-arrays, thus facilitating mass fabrication ofbio-chips. Applicator heads 15 embodying the present invention can beequally employed in subjecting selected areas of a surface to otherprocesses, including, but not limited to, processes for repairingpattern defects on a surface, etching specific areas of a surface,depositing metal on a surface, localizing an electrochemical reactionson a surface, depositing catalytic particles for electroless depositionof metals, deposition glass or latex beads or other particles on asurface; passivating specific areas of a surface, patterning proteins,DNA, cells, or other biological entities on a surface, making assays andstaining cells.

Applicator head 15 comprises a dual conduit system. The apertures 18 and19 of the conduits 1 and 2 are disposed at a distance d from another,that is preferably larger than the diameter of the apertures 18 and 19themselves. The first fluid 3 that is delivered from the deliveryaperture 18 travels along the distance d and is then drawn up into thesecond aperture 19. The device hence works as a dynamic fluid deliverysystem, in that the first fluid 3 is always in motion to confine itsspreading into the environmental fluid 20. Due to the constant flow ofthe first fluid 3, the applicator head 15 can be moved over the surface11 also during the application of the first fluid 3. The major part ofthe first fluid 3 that is expelled from the first aperture 18 onto thesubstrate surface 11 is drawn into the second aperture 19. In the idealcase, the portion of the first fluid that is drawn into the secondaperture 19 is more than 90 percent of the expelled amount of the firstfluid 3. The distance d between the apertures 18 and 19 determines thesize of the resulting pattern 12 on the surface 11. In an applicationwhere the applicator head 15 is not moved during the fluid application,the pattern 12 has hence a length that substantially corresponds to thedistance d. More precisely, if the distance is measured between thecenters of the apertures, the length of the pattern 12 in that directioncorresponds to the distance d plus the distance between the centers andthe distal aperture rim of each of the apertures 18 and 19. In a case inwhich the applicator head 15 is moved and used, for example, like awriting implement in a “pencil-like” fashion, the distance d determinesthe width of the line if moved orthogonally to the line connecting thetwo apertures 18 and 19.

The expulsion of the first fluid 3 from the first aperture 18 occurssynchronously to the sucking of the second fluid 4 into the secondaperture 19, in order to achieve the desired precision of the resultingpattern 12. To ensure that the fluid flow of the second fluid 4 occursat the same time as the fluid flow of the first fluid 3, the flowcontrollers 7 and 8 can be coupled to respond to a single switch-onsignal, or be mechanically coupled. The applicator head 15 is ideallyoperated to draw as much as possible, if not all, of the expelled firstfluid 3 into the second aperture 19.

The device can also be operated to manipulate a particle, such as acell, a bead, a molecule or a nanodevice. Therefore, the applicator head15 is located near the particle that resides on the surface 11 in theenvironmental fluid 20. The first fluid 3 is then moved towards thesurface 11, whereby the particle is removed from the surface 11 anddrawn into the second conduit 2. The applicator head 15 can thereafterbe removed from that position. The particle can in the same, or amodified form, thereafter be deposited at a different location, eitherby moving it into the first conduit 1 and from there to the differentlocation, or by reversing the operation of the applicator head 15 andmoving the second fluid towards the surface 11.

Although illustrative embodiments of the present invention have beendescribed herein, it is to be understood that the invention is notlimited to those precise embodiments, and that various other changes andmodifications may be made by one skilled in the art without departingfrom the scope or spirit of the invention.

1. A device for applying a liquid to a surface immersed in anenvironmental liquid, said device comprising: a first conduit fordirecting a flow of a first liquid towards a surface and a secondconduit for directing a flow of a second liquid away from said surface,wherein said first conduit has a first aperture that is arranged at adistance (d) from a second aperture of said second conduit, said devicefurther comprising one or more of a first flow controller forcontrolling one or more of a first flow rate and a first pressure (p3)of said first liquid, and a second flow controller for controlling oneor more of a second flow rate and a second pressure (p4) of said secondliquid, said first conduit being arranged relative to said secondconduit such that in operation said second liquid comprisessubstantially said first liquid, whereby said device is configured tohydrodynamically confine a flow of a liquid between said first aperture,said second aperture and said immersed surface.
 2. The device of claim1, further comprising one or more of a first liquid container for saidfirst liquid and a second liquid container for said second liquid. 3.The device of claim 1, wherein said first flow controller is furtherconfigured to provide a dispense rate that results in a laminar flow. 4.The device of claim 1, wherein one or more of said first flow controllerand said second flow controller are further configured to respectivelyprovide one or more of first and second pressures (p3, p4) and first andsecond flow rates such that, in operation, said first liquid is drawntowards said second aperture.
 5. The device of claim), furthercomprising a filter for regenerating said first liquid from said secondliquid.
 6. The device of claim 1, further comprising an applicator head,wherein said first conduit and said second conduit are arranged at saidapplicator head.
 7. The device of claim 6, comprising a drive for movingsaid applicator head relative to said surface.
 8. The device of claim 6,wherein at least one of said first aperture and said second aperture ofsaid conduits is arranged in a recession of said applicator head.
 9. Thedevice of claim 8, wherein said first aperture and said second apertureare arranged in said recession, serving as a flow path, and wherein saidflow path is not straight.
 10. The device of claim 1, wherein saiddevice is configured such that said first aperture and said secondaperture can be located at a substantially identical distance from saidsurface.
 11. The device of claim 1, comprising a third conduit fordirecting a flow of a third fluid, wherein said third conduit isconfigured to influence said flow of said first liquid in its flowdirection.
 12. The device of claim 1, comprising a distance element fordetermining said distance between said apertures and said surface. 13.The device of claim 1, wherein said device is of unitary construction.14. A method for applying a first liquid to a surface, said methodcomprising: locating a device proximal to said surface, wherein saiddevice comprises a first conduit for directing a flow of a first liquidtowards a surface and a second conduit for directing a flow of a secondliquid away from said surface, wherein said first conduit has a firstaperture that is arranged at a distance (d) from a second aperture ofsaid second conduit, said device further comprising one or more of afirst flow controller for controlling one or more of a first flow rateand a first pressure (p3) of said first liquid, and a second flowcontroller for controlling one or more of a second flow rate and asecond pressure (p4) of said second liquid, said first conduit beingarranged relative to said second conduit such that in operation saidsecond liquid comprises substantially said first liquid, whereby saiddevice is configured to hydrodynamically confine a flow of a liquidbetween said first aperture, said second aperture and said immersedsurface; and applying said first liquid to said surface via said device.15. The method of claim 14, further comprising a step of varying saidflow of said first liquid during said supply of said first liquid tosaid surface.
 16. The method of claim 14, further comprising a step ofmoving said device relative to said surface with said first liquidcontacting said surface.
 17. The method of claim 16, comprisingorienting said device relative to said surface such that traces of saidfirst liquid produced as said device is moved relative to said surfaceremain one of separate and overlap.
 18. The method of claim 14, whereinsaid step of locating comprises said step of locating an array of aplurality of said devices proximal to said surface; said method furthercomprising said steps of: supplying said first liquid to said surface,in at least one device of said array, flowing said first liquid via aflow path from said first conduit towards said second conduit; andmoving said array relative to said surface with said first liquid ineach aperture contacting with said surface.
 19. The method of claim 18,further comprising a step of varying said flow of said first liquidduring said supply of said first liquid to said surface in at least onedevice of said array.
 20. The method of claim 14, wherein said step oflocating comprises a step of locating said device near a particle insaid environmental liquid, said method further comprising operating saiddevice to remove said particle by means of said first liquid.